6′-Methylpyrido[3,4-b]norhomotropane: synthesis and outstanding potency in relation to the α4β2 nicotinic receptor pharmacophore model

6′-Methylpyrido[3,4-b]norhomotropane [synthesis as the racemate reported here] is more potent at the α4β2 nicotinic receptor than any previous bridged nicotinoid. The two nitrogens and 6′-methyl substituent are superimposable on the two nitrogens and 6-chloro substituent of epibatidine, with the best fit on comparing the chair conformer of the (1R)-pyridonorhomotropane with natural (1R)-epibatidine. In this pharmacophore model, the 6′-methyl substituent may be equivalent to the acetyl methyl of acetylcholine.